tbuckley/cabot-search huggingface dataset:
Characteristics and trends of globally registered malignant pleural mesothelioma clinical trials in the past 27 years.
Authors: Chenguang Guo, Congsen Li, Guoping Shen, HaiYu Zhou
Journal: Journal of Clinical Oncology (2023)

e20544 Background: Malignant pleural mesothelioma (MPM), arising from the serosal lining of the thoracic cavity, is a rare malignancy with limited treatment options and very poor prognosis. Recent progress in immunotherapy and innovative devices have advanced treatment fields of MPM. To help investigators understand the landscape of MPM clinical research, characteristic and trends of globally registered trials in the past decades were analyzed in our study. Methods: This is a cross-sectional analysis of MPM trials registered on ClinicalTrials.gov between January 1996 and December 2022. Characteristics pertaining to trail phase, enrollment number, study design, type, funding source, age of population, trial purpose, and participating country were extracted, and chronological shifts were analyzed. Clinical trial variables were enumerated using descriptive statistics and categorical data were presented as frequencies and percentages. Chi-square trend analysis (Cochran–Armitage trend test) was used to evaluate the trend of MPM trials. Results: 267 registered MPM trials were analyzed involving 40 participating countries among which the United States, the United Kingdom, and Italy were top 3. 8.2% trials were phase 3 and 18.7% were randomized. 74 trials had publications by the December 2022. The trial purposes concerning surgery, radiotherapy, chemotherapy, target therapy, immunotherapy, photodynamic therapy, cryotherapy, tumor treating fields （TTF）and non-anticancer research accounted for 2.6%, 5.2%, 20.2%, 25.5%, 31.1%, 1.1%, 0.7%, 0.7% and 12.7% respectively. In the past 27 years, the numbers of chemotherapy and targeted therapy trials declined while immunotherapy trails steadily escalated (all above p trend &lt; 0.05). There are no significant changes for the trends of each trial phase. 205 drug therapy trials involved 26 cytotoxic drugs, 44 targeted drugs and 11 immune checkpoint inhibitors and 34 other drugs. Pemetrexed-cisplatin with TTF and ipilimumab-nivolumab have changed the frontline treatment space while improvement for regulatory approvals has been far slower in salvage treatment, with the median overall survival all less than 11 months in phase 3 trials. There are no definitive trials that justify the use of predictive biomarkers for systemic therapy in MPM. Conclusions: Immunotherapy and TTF have reshaped the standard of care landscape over the past 27 years. With the enhanced understanding of molecular characteristics and mechanism of MPM, it is anticipated that ongoing immunotherapy combined with target therapy, chemotherapy or other novel treatment can improve the frontline and post-line therapeutic effect.
Clinicopathologic features and outcomes associated with induction regimen intensity among older veterans with myeloma.
Authors: Conor Kirby, George Atweh, Ashley Elizabeth Rosko, Daphne Ruth Friedman, Sarvari Yellapragada, Vishal Vashistha
Journal: Journal of Clinical Oncology (2023)

e20054 Background: More than one third of patients diagnosed with multiple myeloma (MM) are 75 years or older. Though registries and clinical trials have conveyed the disease features across myeloma patients and have confirmed improvement in outcomes with increasing number of frontline induction agents, older patients are disproportionately excluded from these studies. We sought to evaluate the disease characteristics and frontline (FL) induction treatment patterns among older Veterans. Methods: The VA’s Corporate Data Warehouse was queried to identify patients who (1) were diagnosed with MM between January 1, 2016 and December 31, 2019, (2) were 75 years or older at the time of diagnosis, and (3) received at least 1 induction regimen within the VA. Each unique record was reviewed in the VA’s Joint Legacy Viewer, an online platform collectivizing Veteran electronic charts nationwide. Data abstraction was performed to ascertain disease type, cytogenetics, stage, and characteristics of treatment regimen(s) by reviewing provider progress notes and treatment notes. Presence of del(17p), t(4;14), t(14;16), t(14;20), or gain 1q by FISH defined high-risk cytogenetics. Median composite progression-free survival (PFS), defined as the interval between date of FL induction initiation and the earliest date of second induction or death, was computed for Veterans based upon number of drugs in their FL induction regimens. Results: A total of 199 Veterans met selection criteria, with a mean age of 83.0 (SD 4.8) years at start of treatment. Of the 84 patients with documented cytogenetics, 44 (52.3%) had high-risk disease, and 6 (7.1%) had 2 or more deleterious cytogenetic findings. The majority (52.8%) of patients received only 1 induction regimen, and only 44 (22.1%) patients received maintenance therapy following frontline induction. 1 patient underwent autologous stem cell transplant, and 1 was referred for chimeric antigen receptor T-cell therapy. Within FL induction regimen, 104 (52.3%) received 2 drugs and 88 (44.2%) received 3 drugs. Induction therapy selection was unrelated to disease stage (p = 0.556) or cytogenetic risk (p = 0.335), but patients 80 years or older were more likely to receive 2-drug therapy (p = 0.012) than those between 75 and 79 years. No difference in median composite PFS was observed between patients receiving 2 drugs (10.1 [4.5 – 21.7] months) and those receiving 3 drugs (10.7 [5.0 – 20.3] months) (p = 0.733) in FL induction regimen. Conclusions: In a real-world study of older Veterans with MM bearing a high rate of high-risk cytogenetics, the median PFS with FL induction is only 10 months, but a more intensive FL 3-drug induction regimen is not more beneficial than a 2-drug. Less intense treatment planning is most reasonable for geriatric patients. Larger investigations evaluating cytogenetic results across Veterans with MM should be considered.
Comparison of glomerular filtration rate estimating equations in Indian geriatric patients with cancer.
Authors: Vikram Gota, Khushboo A Gandhi, Renita Castelino, Sharath Kumar, Ashish Chavan, Aditi Shirsat, Abhijith Rajaram Rao, Shreya Gattani, Anita Kumar, Anupa Pillai, Arshiya Sehgal, Anant Ramaswamy, Ratan Dhekale, Jyoti Krishnamurthy, Shripad Dinanath Banavali, Rajendra A. Badwe, Kumar Prabhash, Vanita Noronha
Journal: Journal of Clinical Oncology (2023)

e24025 Background: Accurate estimation of glomerular filtration rate (eGFR) is essential for dose calculation of certain anticancer drugs. It is particularly important in older cancer patients because of age-related compromise in renal function. 99m Tc-DTPA plasma clearance for GFR measurement poses practical difficulties in the elderly and is expensive. Therefore, we investigated the predictive accuracy of eight commonly used eGFR equations against 99m Tc-DTPA plasma clearance as the gold standard in Indian geriatric oncology population. Methods: A cross-sectional study was conducted in the geriatric oncology clinic of Tata Memorial Hospital, India, from June 2021 to November 2022. Age, sex, weight, BUN and serum creatinine were obtained from the hospital records. Serum cystatin C was estimated using sandwich ELISA (Sigma, Germany). GFR was estimated using Cockcroft-Gault (CG); 6 variable MDRD; 4 variable MDRD; CKD-EPI creatinine; CKD-EPI cystatin; CKD-EPI creatinine-cystatin; BIS 1; and BIS 2 equations. GFR was also measured by 99m Tc-DTPA plasma technique (Gates’ method). The agreement between different eGFR methods and the measured GFR was analyzed using Bland-Altman test. Results: Out of 311 enrolled patients, 276 patients having full covariate data required for estimation of eGFR by all eight equations were included in the analysis. Majority were males (N = 214). Median age (range) of the patients was 68 (60 – 88) years. Median of measured GFR using 99m Tc-DTPA was 71 (17 – 141) ml/min. The performance i.e., bias and 95% Limit of Agreement (LoA) of eGFR equations against measured GFR is shown in table 1. Overall, the BIS 2 equation with least bias of 0.854 and narrowest 95% LoA (-31.23 to 32.94) had the highest agreement with ‘gold standard’. In fact, BIS 2 performed consistently well across age (60-70, 71-80, 81-90) and BMI (≤18.5, 18.6-24.9, ≥25) groups (data not shown). BIS 2 was followed by CKD-EPIcr-cys and CKD-EPIcys with best estimates of bias and 95% LoA (Table 1). Interestingly, all three equations have cystatin C as a covariate. 4vMDRD had the highest bias (-24.08) and least agreement with DTPA (-86.52 – 38.36). Post hoc analysis showed that 59/115 (51.3%) patients who were cisplatin-ineligible (GFR &lt; 60) based on CG were cisplatin-eligible based on BIS 2, while 19/161 (11.8%) patients who were cisplatin-eligible based on CG were actually ineligible as per BIS 2. Conclusions: Equations derived using cystatin C in general, and BIS 2 in particular, have highest predictive accuracy for GFR estimation in older cancer patients. [Table: see text]
ENLIGHten-01: A phase 1 study of fluorescein-specific (FITC-E2)-CAR T cells in combination with folate-fluorescein (UB-TT170) for osteosarcoma.
Authors: Catherine Michelle Albert, Navin R. Pinto, Mallory Taylor, Ashley Wilson, Stephanie Rawlings-Rhea, Wenjun Huang, Kristy Seidel, Prabha Narayanaswamy,, Stephanie Mgebroff, Christopher Brown, Jacob Garcia, Jeffrey Teoh, Rebecca Alice Gardner, Rimas Orentas, Michael C. Jensen, Julie R. Park
Journal: Journal of Clinical Oncology (2023)

TPS11581 Background: Outcomes for relapsed osteosarcoma (OS) remain poor and there are no systemic therapies that have been shown to provide a survival benefit. Chimeric Antigen Receptor (CAR) T cell immunotherapy involves the adoptive transfer of T-lymphocytes that have been engineered to recognize tumor-specific antigens, resulting in targeted lysis of malignant cells. Folate receptors (FR) are membrane-bound surface proteins that bind folates with high affinity. FRs are overexpressed in OS and have very limited expression in normal tissue. UB-TT170 (Umoja Biopharma) is a small molecule bispecific “adapter” consisting of folate conjugated to fluorescein (FL). It penetrates tumors in minutes and is retained for long periods of time due to high affinity for the FR, while unbound UB-TT170 rapidly clears from the blood and from FR- tissues. We hypothesize that administration of fixed dosing anti-FL(FITC-E2) CAR T cells followed by escalating doses of UB-TT170 will deliver personalized immunotherapy to OS patients. In addition, this approach offers an attractive safety mechanism since administration of NaFL should reverse CAR T cell reactivity. Methods: We designed a Phase I study for young adult (15-30 yr) patients with recurrent/refractory OS to examine the safety and feasibility of administering autologous, peripheral blood-derived T cells that have been genetically modified to express a 2nd generation FL-specific CAR in combination with intra-subject dose escalation of UB-TT170. The primary objective is to identify a recommended dose escalation sequence of UB-TT170 to move forward in clinical development. A 3+3 design will be used to investigate 3 possible dosing sequences. The trial opened in July 2022. As of January 5, 2023, 5 subjects have enrolled and one subject has been treated on dose regimen 1.T cell products have been successfully manufactured for all enrolled subjects. The trial remains open to enrollment. Clinical trial information: NCT05312411 .
Exploring the clinical significance of specific immune-related adverse events (irAE) in patients with melanoma undergoing immune checkpoint inhibitor (ICI) therapy.
Authors: Nethanel Asher, Neta Bar-Hai, Guy Ben-betzalel, Ronen Stoff, Shirly Grynberg, Jacob Schachter, Ronnie Shapira-Frommer
Journal: Journal of Clinical Oncology (2023)

9566 Background: Several studies have demonstrated that patients who experience irAE as a result of ICI treatment, exhibit significantly improved outcomes compared to patients without toxicity. However, data regarding the impact of specific irAE is currently lacking. Methods: This is a real world single-site cohort of advanced melanoma patients who were treated with ICI as first line between 2014 and 2020. This study explores the effects of specific irAE on treatment efficacy. Results: Three hundred and ninety-five (395) patients were treated with either monotherapy anti PD-1 (65.4%), combination ICI (24.3%), or anti CTLA-4 (10.3%). Median age was 68 years (12-99y), and 57% were male. The median follow up was 24.5m. Any-grade irAEs were seen in 72% (n = 299), and 26% experienced high-grade irAE (n = 104). The most frequent irAE were dermatologic (n = 110, 27.8%), vitiligo (n = 48, 12.1%), rheumatologic (n = 68, 17.2%), gastro-intestinal (n = 66, 16.7%), and endocrine (n = 61, 15.4%). The development of irAE was associated with a significantly longer median PFS (19.3m vs 4.5m; HR 0.46, p &lt; 0.001) and median OS (55m vs 16.9m; HR 0.44, p &lt; 0.001). Specific irAE that were significantly associated with survival benefic were rheumatologic (HR 0.34 for PFS, p &lt; 0.001; HR 0.38 for OS, p &lt; 0.001), dermatologic (HR 0.58 for PFS, p &lt; 0.001; HR 0.54 for OS, p = 0.001), vitiligo (HR 0.30 for PFS, p &lt; 0.001; HR 0.29 for OS, p &lt; 0.001) and endocrine (HR 0.6 for PFS, p = 0.01; HR 0.52 for OS, p &lt; 0.001). After adjustment for ECOG performance status, LDH level, type of ICI protocol and M-substage - the rheumatologic, dermatologic and vitiligo irAE remained significant on multivariate analysis for both PFS and OS. Conclusions: The development of rheumatologic, vitiligo and other dermatologic irAE during ICI treatment, is correlated with a noteworthy survival advantage. These irAE may reflect a hyper-activated immune response and thus can serve as meaningful clinical biomarkers.
Peaceful acceptance of illness among older adults with cancer.
Authors: Elizabeth Gilbride, Sofiia Hryniv, William Consagra, Supriya Gupta Mohile, Sule Yilmaz, Eva Culakova, Beverly Canin, Arul Malhotra, Elie G. Dib, Adedayo A. Onitilo, Jeffrey L. Berenberg, Marissa LoCastro, Maya Anand, Allison Magnuson, Kah Poh Loh
Journal: Journal of Clinical Oncology (2023)

12045 Background: Greater illness acceptance is associated with lower levels of psychological distress and higher rates of completion of advance care planning in adults with advanced cancer. However, studies on factors associated with illness acceptance among older adults with advanced cancer are limited and historically have not explored its relationship with caregiver or physician characteristics, despite the important role caregivers and oncologists play in patient illness acceptance. We aimed to evaluate the associations of patient, caregiver, and physician-related factors with illness acceptance among older adults with cancer. Methods: We utilized data from a national geriatric assessment cluster-randomized trial (NCT 02054741; PI: Mohile; funding NCI UG1CA189961). We recruited patients aged 70 years or over with stage III or IV incurable solid tumors or lymphoma and at least one geriatric assessment domain impairment as well as their caregivers. Illness acceptance was assessed using the 5-item Peace, Equanimity, and Acceptance in the Cancer Experience (PEACE) questionnaire (range 5-20). Higher PEACE score indicates greater illness acceptance. Multiple linear regression was used to assess the associations of patient, caregiver, and physician-related variables with PEACE. Variables included patient sociodemographic factors, geriatric assessment variables, and estimated life expectancy; caregiver sociodemographic variables, anxiety, depression, and physical function; and oncologist years in practice and comfort with geriatrics. Results: We included 333 patient-caregiver dyads; mean age (SD) of patients and caregivers, respectively, were 76.8 (5.4) and 66.6 (12.1). Approximately 27%, 26%, and 16% of patients had lung, gastrointestinal, and genitourinary cancers, respectively. Mean PEACE score was 17.4 (2.5), indicating relatively high illness acceptance (Table). On regression analysis, patient psychological impairment domain (including both anxiety and depression) (B=-0.89; p&gt;0.01), patient’s lower estimated life expectancy (≤1 vs. &gt;5 years, B=-1.19, p=0.02), and lower caregiver education attainment (≤high school vs. college; B=-0.86; p&lt;0.01) were associated with a lower illness acceptance. No physician variables were associated with PEACE. Conclusions: A better understanding of illness acceptance and its associated factors can facilitate patient-caregiver dyadic interventions to improve illness acceptance. [Table: see text]
Comparison of lung cancer clinical trials treatment options and standard practice in Brazilian national health system over the last decade.
Authors: Marina Melo, Felippe Lazar Neto, Mateus Trinconi Cunha, Gilberto Castro
Journal: Journal of Clinical Oncology (2023)

e18678 Background: New cancer drugs for metastatic non-small cell (NSCLC) and small cell lung cancer (SCLC) have been approved worldwide in the past decade, but expensive pricing has led to unequal access. Despite being categorized as an upper-middle income country, Brazil's public health system is underfunded and has faced difficulties in incorporating new cancer treatments, which is concerning as two-thirds of the population depend on the public health system for their cancer-related medical needs. We hypothesized that the disparity between the standard of care (SOC) provided in developed nations and the prevailing practices in Brazil's public healthcare system is widening. Methods: We conducted a search of the ClinicalTrials.gov database from January 1 st , 2012 to December 31 th , 2021, for all phase III clinical trials on metastatic lung cancer that had at least one clinical site located in Brazil. We collected data on the experimental arm therapies, planned outcomes, and control arm therapies (used as a proxy for the standard of care worldwide). We then compared the control-arm drug therapy at the trial's start date with the standard practice for lung cancer in the Brazilian Unified Health System (SUS) at that time, using available governmental protocols on lung cancer (PCDT) and recent approvals from the technology health assessment committee (CONITEC). Additionally, we assessed the potential eligibility of patients treating in SUS for second-line therapy trials based on prior required treatments to trial enrollment. We analyzed two time periods: 2012-2016 and 2017-2021. Results: Out of 86 screened trials, 64 were included. 86% of them were on NSCLC, and 67% on first-line settings. Almost half had a biomarker inclusion criterion for enrollment. Immunotherapy was studied most frequently (52%), followed by targeted therapies (36%) and antibody-conjugate drugs (ADC) (9.4%). PD(L)1 was the target of 33% of drug therapies. Compared to 2012-2017, in the 2018-2021 period we observed an increase in available clinical trials (24 vs 40) with similar rates of NSCLC (83% vs. 88%, p = 0.7) and first-line therapies (68 vs 67%, p &gt; 0.9). The proportion of trials with control group therapies better than the standard practice available at the time increased from 8.3% to 38% in the recent time-period (p = 0.011). Among second-line therapy trials, the proportion of trials with mandatory previous therapy unavailable in SUS rose numerically from 12% to 54% (p = 0.085). Conclusions: While the number of trials increased over time, there was a rising proportion of control group therapies better than available standard practice in Brazil. The widening difference between drug therapies in clinical trials and standard cancer treatments creates difficult ethical quandaries for oncologists enrolling patients, and also impacts patient eligibility in advanced settings.
Trajectories of physical well-being among adults with acute myeloid leukemia.
Authors: Marielle Jensen-Battaglia, Michael Sohn, Ying Wang, William Consagra, Marissa LoCastro, Jenae N. Davis, Kathryn Buettner, Soroush Mortaz, Areej El-Jawahri, Kah Poh Loh
Journal: Journal of Clinical Oncology (2023)

e19040 Background: Adults with acute myeloid leukemia (AML) commonly experience physical decline related to their disease and treatment which is associated with negative outcomes. However, physical trajectories differ among patients. Identifying distinct physical trajectories may help guide clinical decision making and supportive care interventions. In this secondary analysis, we examined physical trajectories of patients with AML and factors associated with these trajectories. Methods: We used data from patients with newly diagnosed AML in four clinical trials. Functional Assessment of Cancer Therapy Physical Well-Being sub scale (FACT-PWB, range 0-28) was measured from baseline to day 200, up to 5 timepoints per patient. We used group-based trajectory models (GBTM) weighted for mortality-related drop out to identify groups of patients with similar trajectories of change in FACT-PWB and estimate the association of baseline demographics (age, marital status, education) and clinical factors (AML risk, baseline FACT-PWB, depression, anxiety) with group membership. The number of groups was selected based on clinical interpretability and model fit statistics. Results: We included 343 patients with ≥ 1 FACT-PWB score during up to 200 days of follow-up. Mean age was 65 (SD 12.7), most had intermediate risk AML (178, 52%), received intensive treatment (244, 71%), and died during the follow up period (199, 58%). The GBTM with 4 patterns of change in FACT-PWB showed the best fit for our data (Table). The largest group (Group 2: N = 188, 55%) declined slightly in the first month, then stabilized, while those in the smallest group (Group 1: N = 16, 5%) declined steadily in the first 3 months before improving and stabilizing. Lower baseline FACT-PWB was associated with membership in Group 3: Slight improvement then stable (115, 34%) and Group 4: Steep improvement then stable (24, 7%)), relative to Group 2 (p &lt; .001). Other variables were not associated with group membership. Conclusions: Adults newly diagnosed with AML show distinct patterns of change in their physical well-being after starting treatment. Future studies should measure self-reported and objective physical function in addition to physical well-being in patients with AML, especially with recent change in treatment landscape, to better understand their trajectories. [Table: see text]